Uses of chimeric antigen receptor (car) t-cell therapies in combination with inhibitors of inflammation-related soluble factors

Abstract

Provided herein are uses of chimeric antigen receptors (CARs) for treating a cancer (such as B cell related cancer, e.g., multiple myeloma).

What is claimed is: 
     
         1 . A method of predicting whether a cancer in a human will be responsive to chimeric antigen receptor (CAR) T cells, comprising
 (i) determining the level of one or more inflammation-related soluble factors in serum from the human; and   (ii) if the level of the one or more soluble factors of (i) is similar to that in serum from a patient responsive to chimeric antigen receptor (CAR) T cells, then administering to the human a therapeutically effective dose of the CAR T cells.   
     
     
         2 . A method of treating a cancer in a human in need thereof, comprising determining a level of one or more inflammation-related soluble factors in a serum sample from the human in need thereof, wherein if the level of the one or more inflammation-related soluble factors is similar to the level of the one or more inflammation-related soluble factors in a serum sample from a patient responsive to chimeric antigen receptor (CAR) T cells, the human in need thereof is subsequently provided a therapeutically effective dose of chimeric antigen receptor (CAR) T cells. 
     
     
         3 . A method of treating a cancer in a human in need thereof, comprising:
 a. determining that a level of one or more inflammation-related soluble factors in a serum sample from the human in need thereof is similar to the level of the one or more inflammation-related soluble factors in a serum sample from a patient responsive to chimeric antigen receptor (CAR) T cells;   b. on the basis of the determination in step a, subsequently providing a therapeutically effective dose of chimeric antigen receptor (CAR) T cells to the human in need thereof.   
     
     
         4 . A method of treating a cancer, comprising administering to a human patient diagnosed with cancer a therapeutically effective dose of chimeric antigen receptor (CAR) T cells, wherein a level of one or more inflammation-related soluble factors in a serum sample from the human patient prior to said administration was determined to be similar to a level of the one or more inflammation-related soluble factors in a serum sample from a patient responsive to chimeric antigen receptor (CAR) T cells. 
     
     
         5 . A method of determining whether a patient diagnosed with a cancer should be administered chimeric antigen receptor (CAR) T cells, comprising determining a level of one or more inflammation-related soluble factors in a serum sample from the patient, wherein if the level of one or more inflammation-related soluble factors in the serum sample from the patient is similar to a level of the one or more inflammation-related soluble factors in a serum sample from a patient responsive to chimeric antigen receptor (CAR) T cells, then the patient is a candidate for the CAR T cells. 
     
     
         6 . The method of claim any one of  claims 1 - 5 , wherein the one or more inflammation-related soluble factors are selected from the group consisting of PGF, CD70, TNFRSF4, TNFRSF9 (sCD137 or s4-1BB), DCN, CD83, IL10, PDCD1, IL12, and NCR1. 
     
     
         7 . The method of  claim 6 , wherein the one or more inflammation-related soluble factors are selected from the group consisting of PGF, CD70, TNFRSF9, and CD83. 
     
     
         8 . The method of any one of  claims 1 - 7 , wherein the cancer is multiple myeloma. 
     
     
         9 . The method of any one of  claims 1 - 8 , wherein the CAR T cells are CAR T cells directed to BCMA. 
     
     
         10 . The method of  claim 9 , wherein the CAR T cells directed to BCMA are selected from the group comprising BCMA02, ABECMA©, JCARH125, JNJ-68284528 (LCAR-B38M; protein comprising SEQ ID NO: 265 of 10,934,363 or SEQ ID NO: 300 of WO 2018/028647, either one with or without signal peptide) (Janssen/Legend), P-BCMA-101 (Poseida), PBCAR269A (Poseida), P-BCMA-Allol (Poseida), Allo-715 (Pfizer/Allogene), CT053 (Carsgen), Descartes-08 (Cartesian), PHE885 (Novartis), and CTX120 (CRISPR Therapeutics). 
     
     
         11 . The method of  claim 10 , wherein the CAR T cells directed to BCMA are idecabtagene vicleucel cells (ide-cel). 
     
     
         12 . The method of any one of  claims 1 - 11 , wherein the level of one or more inflammation-related soluble factors is determined by an O-link IO analyte assay. 
     
     
         13 . A method of treating a cancer in a human in need thereof, comprising administering to the human chimeric antigen receptor (CAR) T cells and an antagonist of an inflammation-related soluble factor selected from the group consisting of PGF, CD70, TNFRSF4, TNFRSF9, DCN, CD83, IL10, PDCD1, IL12, and NCR1. 
     
     
         14 . The method of  claim 13 , wherein the inflammation-related soluble factors are selected from the group consisting of PGF, CD70, TNFRSF9, and CD83. 
     
     
         15 . The method of  claim 13  or  14 , wherein the antagonist of an inflammation-related soluble factor is administered to the human at a therapeutically effective amount to reduce the level of the inflammation-related soluble factor in the human to a level of the inflammation-related soluble factor in a patient responsive to chimeric antigen receptor (CAR) T cells. 
     
     
         16 . The method of any one of  claims 13 - 15 , wherein the cancer is multiple myeloma. 
     
     
         17 . The method of any one of  claims 13 - 16 , wherein the CAR T cells are CAR T cells directed to BCMA. 
     
     
         18 . The method of  claim 17 , wherein the CAR T cells directed to BCMA are selected from the group comprising BCMA02, ABECMA©, JCARH125, JNJ-68284528 (LCAR-B38M; protein comprising SEQ ID NO: 265 of 10,934,363 or SEQ ID NO: 300 of WO 2018/028647, either one with or without signal peptide) (Janssen/Legend), P-BCMA-101 (Poseida), PBCAR269A (Poseida), P-BCMA-Allol (Poseida), Allo-715 (Pfizer/Allogene), CT053 (Carsgen), Descartes-08 (Cartesian), PHE885 (Novartis), and CTX120 (CRISPR Therapeutics). 
     
     
         19 . The method of  claim 18 , wherein the CAR T cells directed to BCMA are idecabtagene vicleucel cells (ide-cel). 
     
     
         20 . The method of any one of  claims 13 - 19 , wherein the antagonist of an inflammation-related soluble factor is administered prior to said administration of human chimeric antigen receptor (CAR) T cells. 
     
     
         21 . The method of any one of  claims 13 - 20 , wherein the antagonist of an inflammation-related soluble factor is administered 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days prior to said administration of human chimeric antigen receptor (CAR) T cells. 
     
     
         22 . The method of any one of  claims 13 - 20 , wherein the antagonist of an inflammation-related soluble factor is administered about 1 week, 2 weeks, 3 weeks, or 4 weeks prior to said administration of human chimeric antigen receptor (CAR) T cells. 
     
     
         23 . The method of any one of  claims 13 - 20 , wherein the antagonist of an inflammation-related soluble factor is administered about 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months prior to said administration of human chimeric antigen receptor (CAR) T cells.